Chronic renal disease is a common condition that elevates the risk of complete renal failure, cardiovascular disease and other complications. The prevalence of chronic renal failure has continuously increased in the United States in the last decade. Currently, the only treatment options for renal failure are dialysis and transplantation, both of which are associated with considerable cost. Dialysis, usually performed 3 times per week, impairs the patient's quality of life and does not replace renal functions such as synthesis of erythropoietin and vitamin D. Transplantation, on the other hand, can replace all renal functions, but the rising occurrence of end stage renal disease (ESRD) in the United States continues to outpace the rate of organ donation, as reflected by the fact that the waiting list continues to grow by 3,000 to 4,000 people per year. Furthermore, long-term results of kidney transplantation remain unsatisfactory, mainly because of chronic rejection and complications associated with immunosuppressive medications. Therefore, novel therapies for renal failure are needed.
A major goal of tissue engineering and reconstructive surgery is the restoration of structure and function to damaged organs or tissue. While the body's normal reparative processes can heal small, localized injuries, a large traumatic injury will often overwhelm the body's natural restorative systems and result in a deficit of functional recovery, despite the use of conventional reconstructive modalities. Organ transplantation has become increasingly commonplace in life-threatening situations. Such transplantations involve moving a whole or partial donor organ to replace a recipient's damaged or failing one.
However, problems exist when biological material is transferred from one individual to another. Organ rejection is a significant risk associated with transplantation, even with a good histocompatability match. Immunosuppressive drugs such as cyclosporin and FK506 are usually given to the patient to prevent rejection. These immunosuppressive drugs however, have a narrow therapeutic window between adequate immunosuppression and toxicity. Prolonged immunosuppression can weaken the immune system, which can lead to a threat of infection. In some instances, even immunosuppression is not enough to prevent organ rejection. Another major problem of transplantation is the availability of donor organs. In the United States alone there are about 100,000 people on transplant waiting lists, many of whom will die before an organ becomes available.
Cell-based approaches using tissue engineering and regenerative medicine techniques have offered new therapeutic opportunities for various pathologic conditions. During the past decade, a number of different approaches for engineering renal tissue have been attempted. The goal of each approach was to replace or recover some renal functions. These require several important methodological choices and a number of technical difficulties have been encountered. Although the fundamental principles of cell-based therapies have been demonstrated on multiple tissue systems clinically, it usually necessitates a donor tissue biopsy and ex vivo cell manipulation prior to implantation in vivo. One of the most critical initial steps is the choice of an appropriate cell source. For typical tissue engineering approaches, cells need to be expanded in large quantities, while maintaining uniform activity and remaining pathogen-free. Moreover, the kidney is a extremely complex structure which consists of at least 26 terminally differentiated cell types, including tubular epithelial cells, interstitial cells, glomerular cells and vascular cells.
Most recently, stem cells have been identified as an alternative source of cells for tissue regeneration. However, current protocols for the use of stem cells for regeneration typically require harvesting tissues for cell retrieval, isolation of stem cells, in vitro expansion and/or differentiation of the isolated stem cells, and reimplantation of the manipulated cells into specific tissue sites in vivo for restoration of organ/tissue function.
There exists a need for better methods of tissue regeneration. In particular, new methods of restoring structure and/or function to damaged or failing body structures would satisfy a long-felt therapeutic need.